Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile.

BACKGROUND: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. METHODS: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. RESULTS: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

Comparison of Standard, Cluster, and Rush Allergy Immunotherapy Buildup Protocols.

BACKGROUND: Allergy immunotherapy (AIT) involves a dose-escalation phase following 1 of 3 protocols: standard, cluster, or rush. Although the cluster and rush protocols have been shown to decrease the time to reach maintenance dosing, there is a lack of direct comparison between the protocols. OBJECTIVE: This study aimed to evaluate the differences in time to maintenance dosing and occurrence of adverse reactions among the dose-escalation protocols. METHODS: A retrospective observation study of patients on AIT was conducted. Patients were categorized as participating in the standard, cluster, or rush buildup protocols. Patients on the rush protocol, unlike the standard and cluster protocols, were required to receive prednisone, montelukast, cetirizine, and famotidine on the rush day and first 2 weekly injections thereafter. Variables analyzed include patient demographics, time until maintenance dosing, rate of adverse reactions, treatments required for reactions, and AIT formulation. RESULTS: Data were reviewed on 237 patients on the standard (n = 41), cluster (n = 122), and rush (n = 74) protocols. The maintenance dose was achieved faster with the rush (16.50 weeks) and cluster (19.33 weeks) buildup protocols than the standard (31.09 weeks) protocol (P < .001). There was no statistically significant difference between time to maintenance dosing when comparing the cluster and rush protocols (P = .322). Despite pretreatment with the rush protocol, the rate of systemic reactions was the same for the standard (9.76%), cluster (9.84%), or rush (14.86%) buildup protocols (P = .526). CONCLUSION: Patients on the cluster buildup protocol for AIT achieved maintenance dosing in a comparable time frame as the rush protocol with a similar rate of systemic reactions and without the need for the pretreatment required with rush immunotherapy.

Do patients with metastatic pancreatic adenocarcinoma to the lung have improved survival?

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous disease often diagnosed with synchronous metastatic disease involving the liver. Tumors with extra-abdominal spread that bypass the liver are thought to represent a unique molecular subgroup and those with isolated pulmonary metastatic disease are thought to have a more favorable clinical phenotype. METHOD: We conducted a retrospective review of patients with pathologically confirmed PDAC treated between the years 2007 and 2020 at a Scripps Health hospital. The final study sample (N = 205) included patients with isolated pulmonary metastasis (IL), isolated liver metastasis or synchronous liver and lung metastasis (LL), or metastasis to any site other than the liver or lung (NLL). Primary endpoint was overall survival (OS). Progression-free survival (PFS) and recurrence-free survival (RFS) were analyzed as secondary endpoints. Each survival outcome was analyzed using Cox proportional hazards tests. RESULTS: No statistically significant differences were seen between the three groups in OS, PFS, or RFS. Median OS for the IL group was 561 days, 341 days for the LL group, and 441 days for the NLL group. Median RFS was 748 days for the IL group, 574 days for the LL group, and 545 days for the NLL group. Median PFS was 307 for the IL group, 236 for the LL group, and 265 for the NLL group. When comparing only the IL and LL groups, a statistically significant difference in OS was seen favoring the IL group (HR1.59 LL vs IL [ref], CI 1.04-2.41, p = 0.031) CONCLUSION: Though statistically significant differences in survival outcomes were not seen in our population, there was a trend toward improved survival for patients with isolated lung metastases. When comparing only the IL to LL group, statistically significant overall survival favoring the IL group was seen. These findings highlight a potential prognostic indicator of metastatic PDAC.